A determination of the glomerular filtration rate (GFR) of a patient is frequently requested by physicians to assess renal function. Accurate GFR determinations are important in the appropriate dosing of medication as well as for monitoring of drug induced nephrotoxicity in a patient.
Presently, the most frequently measured parameters indicative of renal function are serum creatinine and urea levels. However, much renal damage must occur before these values become abnormal and early detection is therefore not possible. Although the creatinine clearance test is simple and does not require specialized equipment it is subject to important and well recognized errors, some of which are described below.
The accuracy of glomerular filtration rate (GFR) measurements depends on a "filtration" marker. An ideal filtration marker would be one that is exclusively filtered by the kidney but is neither secreted nor reabsorbed by the renal tubules. Creatinine does not comply with all these requisites. While being filtered by the patient's kidneys, it is also secreted by it. Thus, the glomerular filtration rates obtained by this method are inaccurate.
Urine samples for the creatinine clearance test are typically collected for 24 hours. This is a long period of time that is burdensome to the patient and to the nursing staff and at the same time presents repeated opportunities for error. For example, the patient may forget to save one or more samples, and samples may be spilled and specimens or collection time points may be inaccurately recorded by the staff. These limitations of the creatinine clearance method have led nephrologists to rely on other techniques.
An early alternative was the utilization of inulin for measuring glomerular filtration rates (GFR). Inulin is a natural polysaccharide that is exclusively filtered by the kidney. A world-wide shortage of inulin, however, combined with the cumbersome analysis techniques required by the test have prompted the use of other methods.
An alternative test utilizing Technetium-DTPA (Tc-DTPA) as a filtration marker was introduced. Instead of relying on a chemical assay, such as in the case of the creatinine and inulin tests, the Tc-DTPA test relies on the measurement of radioactivity levels in a sample. While the Tc-DTPA test has proven to be accurate, there are various disadvantages to its implementation. The Tc-DTPA test must be performed in an approved nuclear medicine facility by a registered nuclear technologist. In addition, the material administered to the patient is radioactive and the patient is, therefore, exposed to a small dose of radioactivity. These drawbacks have led to a consideration of other techniques.
Gadolinium-DTPA (Gd-DTPA) is a paramagnetic substance (Magnevist, Berlex Laboratories, Cedar Knolls, N.J.) that was approved in the United States as a magnetic resonance imaging contrast agent in 1988. Since then it has been used as an enhancer of magnetic resonance images in tomography studies (U.S. Pat. No. 4,647,447, the entire content of which is incorporated herein by reference). Gd-DTPA has proven to be an extremely safe and well tolerated agent and has been approved for use in children.
Paramagnetic substances such as Gd-DTPA, however, have never been applied to the measurement of glomerular filtration rates by NMR technology up to the present time.